Drive mechanisms suitable for use in drug delivery devices

ABSTRACT

A drive mechanism suitable for use in drug delivery devices is disclosed. The drive mechanism may be used with injector-type drug delivery devices, such as those permitting a user to set the delivery dose. The drive mechanism may include a housing, a dose dial sleeve, and a drive sleeve. A clutch is configured to permit rotation of the drive sleeve and the dose dial sleeve with respect to the housing when the dose dial sleeve and drive sleeve are coupled through the clutch. Conversely, when the dose dial sleeve and drive sleeve are in a de-coupled state, rotation of the dose dial sleeve with respect to the housing is permitted and rotation of the drive sleeve with respect to the housing is prevented. In the de-coupled state, axial movement of the drive sleeve transfers force in a longitudinal direction for actuation of a drug delivery device.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 11/520,598, filed Sep. 14, 2009, which is a continuationapplication of U.S. patent application Ser. No. 10/790,866, filed Mar.3, 2004, now abandoned, that claims priority to GB 0301822.0 filed Mar.3, 2003, the entire contents of which are incorporated herein byreference.

TECHNICAL FIELD

The present invention relates to drive mechanisms suitable for use indrug delivery devices, in particular pen-type injectors, having dosagesetting means, enabling the administration of medicinal products from amulti-dose cartridge. In particular, the present invention relates tosuch drug delivery devices where a user may set the dose.

BACKGROUND

Such drug delivery devices have application where regular injection bypersons without formal medical training occurs, i.e., patients. This isincreasingly common amongst those having diabetes where self-treatmentenables such persons to conduct effective management of their diabetes.

These circumstances set a number of requirements for drug deliverydevices of this kind. The device must be robust in construction, yeteasy to use in terms of the manipulation of the parts, understanding bya user of its operation and the delivery of the required dose ofmedicament. Dose setting must be easy and unambiguous. In the case ofthose with diabetes, many users will be physically infirm and may alsohave impaired vision requiring the drive mechanism to have lowdispensing force and an easy to read dose setting display. Where thedevice is to be disposable rather than reusable, the device should becheap to manufacture and easy to dispose of (preferably being suitablefor recycling). To meet these requirements the number of parts requiredto assemble the device and the number of material types the device ismade from need to be kept to a minimum.

User operated drug delivery devices are well known within the medicalfield.

In U.S. Pat. No. 5,304,152 a dispensing device is disclosed which has abody length to plunger length ratio of about 1:1 in order to allow thedispensing of relatively large doses. Whilst this device provides manyimprovements over the prior art the easy correction of a set overdoseremains unresolved without either dispensing the set amount of fluid ordismantling the cartridge.

WO 9938554 A2 teaches an injection syringe for apportioning set doses ofa medicine from a cartridge wherein a drive mechanism comprising aunidirectional coupling (i.e., a ratchet) is disclosed which allowscorrection of a set overdose without dispensing the set amount of fluidor requiring the dismantling of the cartridge.

Surprisingly it was found that the drive mechanism according to instantinvention without having a unidirectional coupling provides a valuabletechnical alternative for drive mechanisms, wherein reduced force isneeded to actuate the mechanism. This is achieved by the introduction ofa clutch means as defined by instant invention. The drive mechanismaccording to instant invention further provides the advantage ofintuitive and easy to use correction of a set dose.

SUMMARY

According to a first aspect of the present invention, a drive mechanismfor use in a drug delivery device is provided comprising:

-   -   a housing having a helical thread;    -   a dose dial sleeve having a helical thread engaged with the        helical thread of the said housing;    -   a drive sleeve releasably connected to the said dose dial        sleeve;    -   and a clutch means located between the dose dial sleeve and the        drive sleeve;    -   characterized in that,        -   a) when the dose dial sleeve and the drive sleeve are            coupled, the dose dial sleeve and the drive sleeve are            allowed to rotate with respect to the housing; and        -   b) when the dose dial sleeve and the drive sleeve are            de-coupled, rotation of the dose dial sleeve with respect to            the housing is allowed, whilst rotation of the drive sleeve            with respect to the housing is not allowed, whereby axial            movement of the drive sleeve is allowed so that a force is            transferred in the longitudinal direction to the proximal            end of the drug delivery device.

In a preferred embodiment of the drive mechanism of instant inventionthe said drive mechanism further comprises a piston rod adapted tooperate through the housing and transfer the said force in the saidlongitudinal direction to the proximal end of the drug delivery device.

In another preferred embodiment of the drive mechanism of instantinvention the said dose dial sleeve further comprises a helical thread,which has the same lead as the lead of the helical thread of the saiddrive sleeve.

In a more specific embodiment of instant invention, the drive mechanismfurther comprises a nut, which is rotatable with respect to the drivesleeve and axially displaceable but not rotatable with respect to thehousing.

The term “drug delivery device” according to instant invention shallmean a single-dose or multi-dose, disposable or re-useable devicedesigned to dispense a selected dose of a medicinal product, preferablymultiple selected doses, e.g. insulin, growth hormones, low molecularweight heparins, and their analogues and/or derivatives etc. Said devicemay be of any shape, e.g. compact or pen-type. Dose delivery may beprovided through a mechanical (optionally manual) or electrical drivemechanism or stored energy drive mechanism, such as a spring, etc. Doseselection may be provided through a manual mechanism or electronicmechanism. Additionally, said device may contain components designed tomonitor physiological properties such as blood glucose levels, etc.Furthermore, the said device may comprise a needle or may beneedle-free. In particular, the term “drug delivery device” shall mean adisposable multi-dose pen-type device having mechanical and manual dosedelivery and dose selection mechanisms, which is designed for regularuse by persons without formal medical training such as patients.Preferably, the drug delivery device is of the injector-type.

The term “housing” according to instant invention shall preferably meanany exterior housing (“main housing”, “body”, “shell”) or interiorhousing (“insert”, “inner body”) having a helical thread. The housingmay be designed to enable the safe, correct, and comfortable handling ofthe drug delivery device or any of its mechanism. Usually, it isdesigned to house, fix, protect, guide, and/or engage with any of theinner components of the drug delivery device (e.g., the drive mechanism,cartridge, plunger, piston rod) by limiting the exposure tocontaminants, such as liquid, dust, dirt etc. In general, the housingmay be unitary or a multipart component of tubular or non-tubular shape.Usually, the exterior housing serves to house a cartridge from which anumber of doses of a medicinal product may by dispensed.

In a more specific embodiment of instant invention, the exterior housingis provided with a plurality of maximum dose stops adapted to be abuttedby a radial stop provided on the dose dial sleeve. Preferably, at leastone of the maximum dose stops comprises a radial stop located between ahelical thread and spline means provided at a second end of the housing.Alternatively, at least one of the maximum dose stops comprises a partof a raised window portion provided at a second end of the housing.

The term “engaged” according to instant invention shall particularlymean the interlocking of two or more components of the drivemechanism/drug delivery device, e.g. a spline, thread, or meshed teethconnection, preferably the interlocking of helical threads of components(“threadedly engaged”).

The term “helical thread” according to instant invention shallpreferably mean a full or part thread, e.g., a cylindrical spiralrib/groove, located on the internal and/or external surface of acomponent of the drug delivery device, having an essentially triangularor square or rounded section designed to allow continuous freerotational and/or axial movement between components. Optionally, athread may be further designed to prevent rotational or axial movementof certain components in one direction.

The term “dose dial sleeve” according to instant invention shall mean anessentially tubular component of essentially circular cross-sectionhaving either:

a) both an internal and external thread, or

b) an internal thread, or

c) an external thread.

Preferably, the dose dial sleeve according to instant inventioncomprises a helical thread having a lead, which is similar to,preferably the same as the lead of the helical thread of the drivesleeve. In yet another preferred embodiment the dose dial sleeve isdesigned to indicate a selected dose of a dispensable product. This maybe achieved by use of markings, symbols, numerals, etc., e.g. printed onthe external surface of the dose dial sleeve or an odometer, or thelike.

In a more specific embodiment of instant invention, the dose dial sleeveis provided with a plurality of radially extending members adapted toabout a corresponding plurality of radial stops provided at a second endof the housing.

The term “lead” according to instant invention shall preferably mean theaxial distance a nut would advance in one complete revolution;preferably “lead” shall mean the axial distance through which acomponent having a helical thread, i.e. dose dial sleeve, drive sleeve,piston rod, etc., of the drive mechanism travels during one rotation.Therefore lead is a function of the pitch of the thread of the relevantcomponent.

The term “pitch” according to instant invention shall preferably meanthe distance between consecutive contours on a helical thread, measuredparallel to the axis of the helical thread.

The term “drive sleeve” according to instant invention shall mean anyessentially tubular component of essentially circular cross-section andwhich is further releasably connected to the dose dial sleeve. In apreferred embodiment the drive sleeve is further engaged with the pistonrod.

In a more particular embodiment of instant invention, the drive sleeveis provided at a first end with first and second flanges with anintermediate helical thread between the first and second flanges, havinga nut disposed between the first and second flanges and keyed to thehousing by spline means. Optionally, a first radial stop may be providedon a second face of the nut and a second radial stop may be provided ona first face of the second flange.

The term “releasably connected” according to instant invention shallpreferably mean that two components of instant mechanism or device arereversibly joined to each other, which allows coupling and decoupling,e.g. by means of a clutch.

The term “piston rod” according to instant invention shall mean acomponent adapted to operate through/within the housing, designed totranslate axial movement through/within the drug delivery device,preferably from the drive sleeve to the piston, for the purpose ofdischarging/dispensing an injectable product. Said piston rod may beflexible or not. It may be a simple rod, a lead-screw, a rack and pinionsystem, a worm gear system, or the like. The “piston rod” shall furthermean a component having a circular or non-circular cross-section. It maybe made of any suitable material known by a person skilled in the art.

In a preferred embodiment, the piston rod comprises at least one, morepreferably two, external and/or internal helical threads. In anotherpreferred embodiment of the piston rod according to instant invention, afirst helical thread is located at a first end and a second helicalthread is located at a second end of the said piston rod, whereby thesaid threads may have the same or, preferably, opposite dispositions. Inanother preferred embodiment the piston rod of instant inventioncomprises threads having the same leads at the first and the second end.

In yet another preferred embodiment of instant invention the lead of thefirst helical thread of the piston rod shall be greater than the lead ofthe second helical thread. More preferred, the ratio of the leads of thehelical threads of the said first and the second helical threads is1:1.01 to 1:20, even more preferred 1:1.1 to 1:10. Preferably, one ofthe said threads is designed to engage with the drive sleeve.

Alternatively, in another preferred embodiment of the piston rod ofinstant invention, the piston rod is designed to have attached,optionally by means of a journal bearing, a toothed gear, and whereinsaid toothed gear is designed to mesh with the threads of the drivesleeve and the teeth of a toothed rack, whereby said toothed rack isfixed to the housing.

The term “first end” according to instant invention shall mean theproximal end. The proximal end of the device or a component of thedevice shall mean the end, which is closest to the dispensing end of thedevice.

The term “second end” according to instant invention shall mean thedistal end. The distal end of the device or a component of the deviceshall mean the end, which is furthest away from the dispensing end ofthe device.

The term “clutch means” according to instant invention shall mean anymeans, which releasably connects the dose dial sleeve and the drivesleeve and which is designed to allow rotation of the dose dial sleeveand the drive sleeve with respect to the housing when the dose dialsleeve and the drive sleeve are coupled and, when both are de-coupled,allows rotation of the dose dial sleeve with respect to the housing, butdoes not allow rotation of the drive sleeve with respect to the housingand allows axial movement of the drive sleeve. Preferably, the clutchmeans releasably connects the drive sleeve to the housing. Accordingly,the term clutch means is any clutch engaging for the purpose ofreversibly locking two components in rotation, e.g., by use of axialforces to engage a set of face teeth (saw teeth, dog teeth, crown teeth)or any other suitable frictional faces.

In a more specific embodiment of instant invention, a second end of theclutch means is provided with a plurality of dog teeth adapted to engagewith a second end of the dose dial sleeve.

In an alternative embodiment, the clutch means of instant invention is alocking spring, operable, e.g., by means of a dose dial button, betweena first, relaxed position, in which the dose dial sleeve is locked withrespect to rotation with the drive sleeve and a second, deformedposition, in which the dose dial sleeve is locked with respect torotation with the housing.

In still another embodiment of instant invention, the drive mechanismfurther comprises a clicker means, optionally disposed between theclutch means and spline means provided on the housing.

Optionally, the clicker means comprises a sleeve provided at a first endwith a helically extending arm, a free end of the arm having a toothedmember, and at a second end with a plurality of circumferentiallydirected saw teeth adapted to engage a corresponding plurality ofcircumferentially saw teeth provided on the clutch means. Alternatively,the clicker means comprises a sleeve provided at a first end with atleast one helically extending arm and at least one spring member, a freeend of the arm having a toothed member, and at a second end with aplurality of circumferentially directed saw teeth adapted to engage acorresponding plurality of circumferentially directed saw teeth providedon the clutch means.

In still another embodiment of the drive mechanism of the invention, thedrive mechanism is provided with a first stop means, preferably in theform of an external flange on the dose dial sleeve, adapted to engagelimiting means associated with the housing, preferably in the form of aninternal flange in the housing, to limit the maximum dose which can bedialed. In yet another embodiment of the drive mechanism of theinvention, the drive mechanism is further provided with a second stopmeans, preferably in the form of an external flange on the drive sleeve,adapted to engage limiting means, preferably in the form of a limitingnut keyed to the housing and mounted for rotation on an externalthreaded section of the drive sleeve, to provide an end of life stop.

A second aspect of instant invention provides an assembly for use in adrug delivery device comprising the drive mechanism according to instantinvention.

A third aspect of the present invention provides a drug delivery devicecomprising the drive mechanism or the assembly according to instantinvention.

A fourth aspect of the present invention provides a method of assemblinga drug delivery device comprising the step of providing a drivemechanism or an assembly according to instant invention.

A fifth aspect of instant invention is the use of a drug delivery deviceaccording to instant invention for dispensing a medicinal productpreferably dispensing a pharmaceutical formulation (e.g. solution,suspension etc.) comprising an active compound selected from the groupconsisting of insulin, growth hormone, low molecular weight heparin,their analogues and their derivatives.

BRIEF DESCRIPTION OF THE FIGURES

Without any limitation, the instant invention will be explained ingreater detail below in connection with a preferred embodiment and withreference to the drawings in which:

FIG. 1 shows a sectional view of a first embodiment of the drug deliverydevice in accordance with the present invention in a first, cartridgefull, position;

FIG. 2 shows a sectional view of the drug delivery device of FIG. 1 in asecond, maximum first dose dialed, position;

FIG. 3 shows a sectional view of the drug delivery device of FIG. 1 in athird, maximum first dose dispensed, position;

FIG. 4 shows a sectional view of the drug delivery device of FIG. 1 in afourth, final dose dialed, position;

FIG. 5 shows a sectional view of the drug delivery device of FIG. 1 in afifth, final dose dispensed, position;

FIG. 6 shows a cut-away view of a first detail of the drug deliverydevice of FIG. 1;

FIG. 7 shows a partially cut-away view of a second detail of the drugdelivery device of FIG. 1;

FIG. 8 shows a partially cut-away view of a third detail of the drugdelivery device of FIG. 1;

FIG. 9 shows the relative movement of parts of the drug delivery deviceshown in FIG. 1 during dialing up of a dose;

FIG. 10 shows the relative movement of parts of the drug delivery deviceshown in FIG. 1 during dialing down of a dose;

FIG. 11 shows the relative movement of parts of the drug delivery deviceshown in FIG. 1 during dispensing of a dose;

FIG. 12 shows a partially cut-away view of the drug delivery device ofFIG. 1 in the second, maximum first dose dialed, position;

FIG. 13 shows a partially cut-away view of the drug delivery device ofFIG. 1 in the fourth, final dose dialed, position;

FIG. 14 shows a partially cut-away view of the drug delivery device ofFIG. 1 in one of the first, third or fifth positions;

FIG. 15 shows a cut-away view of a first part of a main housing of thedrug delivery device of FIG. 1; and

FIG. 16 shows a cut-away view of a second part of the main housing ofthe drug delivery device of FIG. 1;

FIG. 17 shows a sectional view of a second embodiment of the drivemechanism according to instant invention in a first, cartridge full,position.

FIG. 18 shows a sectional side view of a third embodiment of the drugdelivery device in accordance with the present invention in a first,cartridge full, position;

FIG. 19 shows a sectional side view of the drug delivery device of FIG.18 in a second, maximum first dose dialed, position;

FIG. 20 shows a sectional side view of the drug delivery device of FIG.18 in a third, maximum first dose dispensed, position;

FIG. 21 shows a sectional side view of the drug delivery device of FIG.18 in a fourth, final dose dialed, position;

FIG. 22 shows a sectional side view of the drug delivery device of FIG.18 in a fifth, final dose dispensed, position;

FIG. 23 shows a fragment of the drug delivery device of FIG. 18 in alarger scale and

FIG. 24 shows a further fragment of the drug delivery device of FIG. 18in a larger scale.

DETAILED DESCRIPTION Example 1

Referring first to FIGS. 1 to 5, there is shown a drug delivery devicein accordance with the present invention in a number of positions.

The drug delivery device comprises a housing having a first cartridgeretaining part 2, and second main (exterior) housing part 4. A first endof the cartridge retaining means 2 and a second end of the main housing4 are secured together by retaining features 6. In the illustratedembodiment, the cartridge retaining means 2 is secured within the secondend of the main housing 4.

A cartridge 8 from which a number of doses of a medicinal product may bedispensed is provided in the cartridge retaining part 2. A piston 10 isretained in a first end of the cartridge 8.

A removable cap 12 is releasably retained over a second end of thecartridge retaining part 2. In use the removable cap 12 can be replacedby a user with a suitable needle unit (not shown). A replaceable cap 14is used to cover the cartridge retaining part 2 extending from the mainhousing 4. Preferably, the outer dimensions of the replaceable cap 14are similar or identical to the outer dimensions of the main housing 4to provide the impression of a unitary whole when the replaceable cap 14is in position covering the cartridge retaining part 2.

In the illustrated embodiment, an insert 16 is provided at a first endof the main housing 4. The insert 16 is secured against rotational orlongitudinal motion. The insert 16 is provided with a threaded circularopening 18 extending therethrough. Alternatively, the insert may beformed integrally with the main housing 4 having the form of a radiallyinwardly directed flange having an internal thread.

A first thread 19 extends from a first end of a piston rod 20. Thepiston rod 20 is of generally circular section. The first end of thepiston rod 20 extends through the threaded opening 18 in the insert 16.A pressure foot 22 is located at the first end of the piston rod 20. Thepressure foot 22 is disposed to abut a second end of the cartridgepiston 10. A second thread 24 extends from a second end of the pistonrod 20. In the illustrated embodiment the second thread 24 comprises aseries of part threads rather than a complete thread. The illustratedembodiment is easier to manufacture and helps to reduce the overallforce required for a user to actuate the device when dispensing themedicinal product.

The first thread 19 and the second thread 24 are oppositely disposed.The second end of the piston rod 20 is provided with a receiving recess26.

A drive sleeve 30 extends about the piston rod 20. The drive sleeve 30is generally cylindrical. The drive sleeve 30 is provided at a first endwith a first radially extending flange 32. A second radially extendingflange 34 is provided spaced a distance along the drive sleeve 30 fromthe first flange 32. An intermediate thread 36 is provided on an outerpart of the drive sleeve 30 extending between the first flange 32 andthe second flange 34. A helical groove (thread) 38 extends along theinternal surface of the drive sleeve 30. The second thread 24 of thepiston rod 20 is adapted to work within the helical groove 38.

A first end of the first flange 32 is adapted to conform to a secondside of the insert 16.

A nut 40 is located between the drive sleeve 30 and the main housing 4,disposed between the first flange 32 and the second flange 34. In theillustrated embodiment the nut 40 is a half-nut. This assists in theassembly of the device. The nut 40 has an internal thread matching theintermediate thread 36. The outer surface of the nut 40 and an internalsurface of the main housing 4 are keyed together by splines 42 (FIGS.10, 11, 15 and 16) to prevent relative rotation between the nut 40 andthe main housing 4, while allowing relative longitudinal movementtherebetween.

A shoulder 37 is formed between a second end of the drive sleeve 30 andan extension 38 provided at the second end of the drive sleeve 30. Theextension 38 has reduced inner and outer diameters in comparison to theremainder of the drive sleeve 30. A second end of the extension 38 isprovided with a radially outwardly directed flange 39.

A clicker 50 and a clutch 60 are disposed about the drive sleeve 30,between the drive sleeve 30 and a dose dial sleeve 70 (described below).

The clicker 50 is located adjacent the second flange 34 of the drivesleeve 30. The clicker 50 is generally cylindrical and is provided at afirst end with a flexible helically extending arm 52 (FIG. 6). A freeend of the arm 52 is provided with a radially directed toothed member54. A second end of the clicker 50 is provided with a series ofcircumferentially directed saw teeth 56 (FIG. 7). Each saw toothcomprises a longitudinally directed surface and an inclined surface.

In an alternative embodiment (not shown) the clicker further includes atleast one spring member. The at least one spring member assists in theresetting of the clutch 60 following dispense.

The clutch 60 is located adjacent the second end of the drive sleeve 30.The clutch 60 is generally cylindrical and is provided at a first endwith a series of circumferentially directed saw teeth 66 (FIG. 7). Eachsaw tooth comprises a longitudinally directed surface and an inclinedsurface. Towards the second end 64 of the clutch 60 there is located aradially inwardly directed flange 62. The flange 62 of the clutch 60 isdisposed between the shoulder 37 of the drive sleeve 30 and the radiallyoutwardly directed flange 39 of the extension 38. The second end of theclutch 60 is provided with a plurality of dog teeth 65 (FIG. 8). Theclutch 60 is keyed to the drive sleeve 30 by way of splines (not shown)to prevent relative rotation between the clutch 60 and the drive sleeve30.

In the illustrated embodiment, the clicker 50 and the clutch. 60 eachextend approximately half the length of the drive sleeve 30. However, itwill be understood that other arrangements regarding the relativelengths of these parts are possible.

The clicker 50 and the clutch 60 are engaged as shown in FIG. 7.

A dose dial sleeve 70 is provided outside of the clicker 50 and clutch60 and radially inward of the main housing 4. A helical groove 74 isprovided about an outer surface of the dose dial sleeve 70.

The main housing 4 is provided with a window 44 through which a part ofthe outer surface of the dose dial sleeve may be seen. The main housing4 is further provided with a helical rib (thread) 46, adapted to beseated in the helical groove (thread) 74 on the outer surface of thedose dial sleeve 70. The helical rib 46 extends for a single sweep ofthe inner surface of the main housing 4. A first stop 100 is providedbetween the splines 42 and the helical rib 46 (FIG. 15). A second stop102, disposed at an angle of 180° to the first stop 100 is formed by aframe surrounding the window 44 in the main housing 4 (FIG. 16).

Conveniently, a visual indication of the dose that may be dialed, forexample reference numerals (not shown), is provided on the outer surfaceof the dose dial sleeve 70. The window 44 conveniently only, allows tobe viewed a visual indication of the dose currently dialed.

A second end of the dose dial sleeve 70 is provided with an inwardlydirected flange in the form of a number of radially extending members75. A dose dial grip 76 is disposed about an outer surface of the secondend of the dose dial sleeve 70. An outer diameter of the dose dial grip76 preferably corresponds to the outer diameter of the main housing 4.The dose dial grip 76 is secured to the dose dial sleeve 70 to preventrelative movement therebetween. The dose dial grip 76 is provided with acentral opening 78. An annular recess 80 located in the second end ofthe dose dial grip 76 extends around the opening 78.

A button 82 of generally ‘T’ section is provided at a second end of thedevice. A stem 84 of the button 82 may extend through the opening 78 inthe dose dial grip 76, through the inner diameter of the extension 38 ofthe drive sleeve 30 and into the receiving recess 26 of the piston rod20. The stem 84 is retained for limited axial movement in the drivesleeve 30 and against rotation with respect thereto. A head 85 of thebutton 82 is generally circular. A skirt 86 depends from a periphery ofthe head 85. The skirt 86 is adapted to be seated in the annular recess80 of the dose dial grip 76.

Operation of the drug delivery device in accordance with the presentinvention will now be described. In FIGS. 9, 10 and 11 arrows A, B, C,D, E, F and G represent the respective movements of the button 82, thedose dial grip 76, the dose dial sleeve 70, the drive sleeve 30, theclutch 60, the clicker 50 and the nut 40.

To dial a dose (FIG. 9) a user rotates the dose dial grip 76 (arrow B).With the clicker 50 and clutch 60 engaged, the drive sleeve 30, theclicker 50, the clutch 60 and the dose dial sleeve 70 rotate with thedose dial grip 76.

Audible and tactile feedback of the dose being dialed is provided by theclicker 50 and the clutch 60. Torque is transmitted through the sawteeth 56,66 between the clicker 50 and the clutch 60. The flexible arm52 deforms and drags the toothed member 54 over the splines 42 toproduce a click. Preferably, the splines 42 are disposed such that eachclick corresponds to a conventional unit dose, or the like.

The helical groove 74 on the dose dial sleeve 70 and the helical groove38 in the drive sleeve 30 have the same lead. This allows the dose dialsleeve 70 (arrow C) to extend from the main housing 4 and the drivesleeve 30 (arrow D) to climb the piston rod 20 at the same rate. At thelimit of travel, a radial stop 104 (FIG. 12) on the dose dial sleeve 70engages either the first stop 100 or the second stop 102 provided on themain housing 4 to prevent further movement. Rotation of the piston rod20 is prevented due to the opposing directions of the overhauled anddriven threads on the piston rod 20.

The nut 40, keyed to the main housing 4, is advanced along theintermediate thread 36 by the rotation of the drive sleeve 30 (arrow D).When the final dose dispensed position (FIGS. 4, 5 and 13) is reached, aradial stop 106 formed on a second surface of the nut 40 abuts a radialstop 108 on a first surface of the second flange 34 of the drive sleeve30, preventing both the nut 40 and the drive sleeve 30 from rotatingfurther.

In an alternative embodiment (not shown) a first surface of the nut 40is provided with a radial stop for abutment with a radial stop providedon a second surface of the first flange 32. This aids location of thenut 40 at the cartridge full position during assembly of the drugdelivery device.

Should a user inadvertently dial beyond the desired dosage, the drugdelivery device allows the dosage to be dialed down without dispense ofmedicinal product from the cartridge (FIG. 10). The dose dial grip 76 iscounter rotated (arrow B). This causes the system to act in reverse. Theflexible arm 52 preventing the clicker 50 from rotating. The torquetransmitted through the clutch 60 causes the saw teeth 56,66 to rideover one another to create the clicks corresponding to dialed dosereduction. Preferably the saw teeth 56,66 are so disposed that thecircumferential extent of each saw tooth corresponds to a unit dose.

When the desired dose has been dialed, the user may then dispense thisdose by depressing the button 82 (FIG. 11). This displaces the clutch 60axially with respect to the dose dial sleeve 70 causing the dog teeth 65to disengage. However the clutch 60 remains keyed in rotation to thedrive sleeve 30. The dose dial sleeve 70 and associated dose dial grip76 are now free to rotate (guided by the helical rib 46 located inhelical groove 74).

The axial movement deforms the flexible arm 52 of the clicker 50 toensure the saw teeth 56,66 cannot be overhauled during dispense. Thisprevents the drive sleeve 30 from rotating with respect to the mainhousing 4 though it is still free to move axially with respect thereto.This deformation is subsequently used to urge the clicker 50, and theclutch 60, back along the drive sleeve 30 to restore the connectionbetween the clutch 60 and the dose dial sleeve 70 when pressure isremoved from the button 82.

The longitudinal axial movement of the drive sleeve 30 causes the pistonrod 20 to rotate though the opening 18 in the insert 16, thereby toadvance the piston 10 in the cartridge 8. Once the dialed dose has beendispensed, the dose dial sleeve 70 is prevented from further rotation bycontact of a plurality of members 110 (FIG. 14) extending from the dosedial grip 76 with a corresponding plurality of stops 112 formed in themain housing 4 (FIGS. 15 and 16). In the illustrated embodiment, themembers 110 extend axially from the dose dial grip 76 and have aninclined end surface. The zero dose position is determined by theabutment of one of the axially extending edges of the members 110 with acorresponding stop 112.

Example 2

In another embodiment of the invention (FIG. 17) there is seen a drivemechanism comprising a second main housing 4′ having a first end and asecond end. A cartridge, containing medicinal product, can be mounted tothe first end of the second main housing 4′ and retained by any suitablemeans. The cartridge and its retaining means are not shown in theillustrated embodiment. The cartridge may contain a number of doses of amedicinal product and also typically contains a displaceable piston.Displacement of the piston causes the medicinal product to be expelledfrom the cartridge via a needle (also not shown).

In the illustrated embodiment, an insert 16′ is provided within the mainhousing 4′. The insert 16′ is secured against rotational and axialmotion with respect to the second main housing 4′. The insert 16′ isprovided with a threaded circular opening extending therethrough.Alternatively, the insert may be formed integrally with the second mainhousing 4′.

An internal housing 154 is also provided within the second main housing4′. The internal housing 154 is secured against rotational and axialmotion with respect to the second main housing 4′. The internal housing154 is provided with a circular opening extending through its length inwhich a series of longitudinally directed splines are formed. A helicalthread 150 extends along the outer cylindrical surface of the internalhousing 154. Alternatively, the internal housing may be formedintegrally with the second main housing 4′ and/or with the insert 16′.

A first thread 19′ extends from a first end of a piston rod 20′. Thepiston rod 20′ is of generally circular section. The first end of thepiston rod 20′ extends through the threaded opening in the insert 16′and the first thread 19′ of the piston rod 20′ is engaged with thethread of the insert 16′. A pressure foot 22′ is located at the firstend of the piston rod 20′. The pressure foot 22′ is disposed to abut acartridge piston (not shown). A second thread 24′ extends from a secondend of the piston rod 20′. The first thread 19′ and the second thread24′ are oppositely disposed.

A drive sleeve 30′ extends about the piston rod 20′. The drive sleeve30′ is generally cylindrical. The drive sleeve 30′ is provided at afirst end with a first radially extending flange 32′. A second radiallyextending flange 34′ is provided, spaced a distance along the drivesleeve 30′ from the first flange 32′. An external helical thread (notshown) is provided on the outer part of the drive sleeve 30′ extendingbetween the first flange 32′ and the second flange 34′. An internalhelical thread extends along the internal surface of the drive sleeve30′. The second thread 24′ of the piston rod 20′ is engaged with theinternal helical thread of the drive sleeve 30′.

A nut 40′ is located between the drive sleeve 30′ and the internalhousing 154, disposed between the first flange 32′ and the second flange34′ of the drive sleeve 30′. The nut 40′ can be either a ‘half-nut’ or a‘full-nut’. The nut 40′ has an internal thread that is engaged with theexternal helical thread of the drive sleeve 30′. The outer surface ofthe nut 40′ and an internal surface of the internal housing 154 arekeyed together by means of longitudinally directed splines to preventrelative rotation between the nut 40′ and the internal housing 154,while allowing relative longitudinal movement therebetween.

A clicker 50′ and a clutch 60′ are disposed about the drive sleeve 30′,between the drive sleeve 30′ and the internal housing 154.

The clicker 50′ is located adjacent the second flange 34′ of the drivesleeve 30′. The clicker 50′ includes at least one spring member (notshown). The clicker 50′ also includes a set of teeth (not shown) havinga triangular profile disposed towards the second end of the drivemechanism. When compressed, the at least one spring member of theclicker 50′ applies an axial force between the flange 34′ of the drivesleeve 30′ and the clutch 60′. The outer surface of the clicker 50′ andan internal surface of the internal housing 154 are keyed together bymeans of longitudinally directed splines to prevent relative rotationbetween the clicker 50′ and the internal housing 154, while allowingrelative longitudinal movement therebetween.

The clutch 60′ is located adjacent the second end of the drive sleeve30′. The clutch 60′ is generally cylindrical and is provided at its'first end with a plurality of teeth of triangular profile disposed aboutthe circumference (not shown), that act upon the teeth of the clicker50′. Towards the second end of the clutch 60′ there is located ashoulder 158. The shoulder 158 of the clutch 60′ is disposed between theinternal housing 154 and a radially inwardly directed flange of the dosedial grip 76′ (described below). The shoulder 158 of the clutch 60′ isprovided with a plurality of dog teeth (not shown) extending in thedirection of the second end of the drive mechanism. The clutch 60′ iskeyed to the drive sleeve 30′ by way of splines (not shown) to preventrelative rotation between the clutch 60′ and the drive sleeve 30′.

A dose dial sleeve 70′ is provided outside of the internal housing 154and radially inward from the second main housing 4′. A helical thread isprovided on an inner surface of the dose dial sleeve 70′. The helicalthread of the dose dial sleeve 70′ is engaged with the helical thread150 of the internal housing 154.

The second main housing 4′ is provided with a window (not shown) throughwhich part of the outer surface of the dose dial sleeve 70′ may beviewed. Conveniently, a visual indication of the dose that may bedialed, for example reference numerals (not shown), is provided on theouter surface of the dose dial sleeve 70′. Conveniently, the window ofthe second main housing 4′ allows only the dose that is currently dialedto be viewed.

A dose dial grip 76′ is located towards the second end of the drivemechanism. The dose dial grip 76′ is secured against rotational andaxial motion within respect to the dose dial sleeve 70′. The dose dialgrip 76′ is provided with a radially inwardly directed flange 160. Theradially inwardly directed flange 160 of the dose dial grip 76′ isprovided with a plurality of dog teeth (not shown) extending in thedirection of the first end of the drive mechanism to abut the dog teethof the clutch 60′. Coupling and decoupling of the dog teeth of the dosedial grip 76′ with the dog teeth of the clutch 60′ provides a releasableclutch between the dose dial grip 76′ and the clutch 60′.

A button 82′ of generally ‘T’ shaped cross-section is provided at asecond end of the drive mechanism. A cylindrical feature of the button82′ extends towards the first end of the drive mechanism, through anopening in the dose dial grip 76′ and into a recess in the drive sleeve30′. The cylindrical feature of the button 82′ is retained for limitedaxial movement in the drive sleeve 30′ and against rotation with respectthereto. The cylindrical feature of the button 82′ has lugs extendingradially (not shown) that abut the second surface of the shoulder 158 ofthe clutch 60′. The second end of the button 82′ is generally circularand has a cylindrical skirt about its' periphery that descends towardsthe first end of the drive mechanism. The skirt of the button 82′ islocated radially inward from the dose dial grip 76′.

Operation of the drive mechanism in accordance with the presentinvention will now be described.

To dial a dose, a user rotates the dose dial grip 76′. The spring memberof the clicker 50′ applies an axial force to the clutch 60′ in thedirection of the second end of the drive mechanism. The force exerted bythe spring member of the clicker 50′ couples the dog teeth of the clutch60′ to the dog teeth of the dose dial grip 76′ for rotation. As the dosedial grip 76′ is rotated, the associated dose dial sleeve 70′, the drivesleeve 30′ and the clutch 60′ all rotate in unison.

Audible and tactile feedback of the dose being dialed is provided by theclicker 50′ and the clutch 60′. As the clutch 60′ is rotated, torque istransmitted from the teeth at the first end of the clutch 60′ and theteeth of the clicker 50′. The clicker 50′ cannot rotate with respect tothe internal housing 154, so the at least one spring member of theclicker 50′ deforms allowing the teeth of the clutch 60′ to jump overthe teeth of the clicker 50′ producing an audible and tactile ‘click’.Preferably, the teeth of the clicker 50′ and the teeth of the clutch 60′are disposed such that each ‘click’ corresponds to a conventional unitof the medicinal product, or the like.

The helical thread of the dose dial sleeve 70′ and the internal helicalthread of the drive sleeve 30′ have the same lead. This allows the dosedial sleeve 70′ to advance along the thread 150 of the internal housing154 at the same rate as the drive sleeve 30′ advances along the secondthread 24′ of the piston rod 20′. Rotation of the piston rod 20′ isprevented due to the opposing direction of the first thread 19′ and thesecond thread 24′ of the piston rod 20′. The first thread 19′ of thepiston rod 20′ is engaged with the thread of the insert 16′ and so thepiston rod 20′ does not move with respect to the second main housing 4′while a dose is dialed.

The nut 40′, keyed to the internal housing 154, is advanced along theexternal thread of the drive sleeve 30′ by the rotation of the drivesleeve 30′. When a user has dialed a quantity of medicinal product thatis equivalent to the deliverable volume of the cartridge, the nut 40′reaches a position where it abuts the second flange 34′ of the drivesleeve 30′. A radial stop formed on the second surface of the nut 40′contacts a radial stop on the first surface of the second flange 34′ ofthe drive sleeve 30′, preventing both the nut 40′ and the drive sleeve30′ from being rotated further.

Should a user inadvertently dial a quantity greater than the desireddosage, the drive mechanism allows the dosage to be corrected withoutdispense of medicinal product from the cartridge. The dose dial grip 76′is counter-rotated. This causes the system to act in reverse. The torquetransmitted through the clutch 60′ causes the teeth at the first end ofthe clutch 60′ to ride over the teeth of the clicker 50′ to create theclicks corresponding to the dialed dose reduction.

When the desired dose has been dialed, the user may then dispense thisdose by depressing the button 82′ in the direction of the first end ofthe drive mechanism. The lugs of the button 82′ apply pressure to thesecond surface of the shoulder 158 of the clutch 60′, displacing theclutch 60′ axially with respect to the dose dial grip 76′. This causesthe dog teeth on the shoulder 158 of the clutch 60′ to disengage fromthe dog teeth of the dose dial grip 76′. However, the clutch 60′ remainskeyed in rotation to the drive sleeve 30′. The dose dial grip 76′ andassociated dose dial sleeve 70′ are now free to rotate (guided by thehelical thread 150 of the internal housing 154).

The axial movement of the clutch 60′ deforms the spring member of theclicker 50′ and couples the teeth at the first end of the clutch 60′ tothe teeth of the clicker 50′ preventing relative rotation therebetween.This prevents the drive sleeve 30′ from rotating with respect to theinternal housing 154, though it is still free to move axially withrespect thereto.

Pressure applied to the button 82′ thus causes the dose dial grip 76′and the associated dose dial sleeve 70′ to rotate into the second mainhousing 4′. Under this pressure the clutch 60′, the clicker 50′ and thedrive sleeve 30′ are moved axially in the direction of the first end ofthe drive mechanism, but they do not rotate. The axial movement of thedrive sleeve 30′ causes the piston rod 20′ to rotate though the threadedopening in the insert 16′, thereby to advance the pressure foot 22′.This applies force to the piston, causing the medicinal product to beexpelled from the cartridge. The selected dose is delivered when thedose dial grip 76′ returns to a position where it abuts the second mainhousing 4′.

When pressure is removed from the button 82′, the deformation of thespring member of the clicker 50′ is used to urge the clutch 60′ backalong the drive sleeve 30′ to re-couple the dog teeth on the shoulder158 of the clutch 60′ with the dog teeth on the dose dial grip 76′. Thedrive mechanism is thus reset in preparation to dial a subsequent dose.

Example 3

Referring to FIGS. 18 to 22 there may be seen a drug delivery device inaccordance with the present invention. The drug delivery devicecomprises a two-part housing 2″ within which are located a cartridge 4″containing a medicinal product, means for setting or selecting the doseof medicinal product to be expelled and means for expelling the selecteddose of medicinal product. The housing 2″ is generally cylindrical inshape and houses a rack 6″ to be described in more detail below. Thecartridge 4″ is located within a first part 8″ of the housing 2″. Thedose setting means and the means for expelling the selected dose ofmedicinal product are retained, that is held, within a second part 10″of the housing 2″. The first part 8″ of the housing 2″ and the secondpart 10″ of the housing 2″ may be secured together by any suitablemeans.

The cartridge 4″ may be secured in position in the first part 8″ of thehousing 2″ by any suitable means. A needle unit may be secured to afirst end of the cartridge 4″. A temporary covering 12″ is shown in thisposition in the Figures. The cartridge 4″ further comprises adisplaceable piston 14″. Advancing the piston 10″ towards the first endof the cartridge 4″ causes the medicinal product to be expelled from thecartridge 4″ through the needle unit. A cap 16″ is provided to cover theneedle unit when the drug delivery device is not in use. The cap 16″ maybe releasably secured to the 1 housing 2″ by any suitable means.

The dose setting means and the means for expelling the selected dose ofmedicinal product will now be described in more detail. The rack 6″ islocated within a drive sleeve 18″ located within the housing 2″ and isfixed both axially and rotationally with respect to the housing 2″ byany suitable means. The drive sleeve 18″ comprises an internallythreaded portion 20″, which extends along substantially the entireinternal surface of the sleeve. An internal toothed gear 22″ is locatedwithin the drive sleeve 18″ and has helical teeth which match the pitchof the internal thread of the drive sleeve 18″. The internal thread ofthe drive sleeve 18″ is a multistart thread with a lead which is thesame as the lead of the helical thread of the dose dial sleeve, whichwill be described later. The drive sleeve 18″ terminates in anexternally threaded section 24″ which extends from an end of the sleeveas far as an external circumferential flange 26″ which projects from thedrive sleeve 18″. A limiting nut 28″ is mounted for rotation on theexternally threaded section 24″ of the sleeve 14″. The limiting nut 28″is keyed to the housing 2″ by means of a plurality of longitudinallyextending splines 30″ which extend along the internal surface of thefirst portion 8″ of the housing 2″. In the illustrated embodiment, thelimiting nut 28″ is shown as a half-nut, but a full nut could be used.

A piston rod 32″ is provided extending along the length of the rack 6″and through a hole in the end of the rack 6″. The piston rod 32″ isgenerally elongate and is provided with a pressure foot 34″. In use thepressure foot 34″ is disposed to abut the cartridge piston 14″. Thetoothed gear 22″ is mounted on the end of the piston rod 32″ remote fromthe pressure foot 34″ in a journal bearing (not shown).

A dose dial sleeve 36″ of generally cylindrical form comprises a firstsection 38″ of first diameter and a second section 40″ of larger seconddiameter. The first section is located within the housing 2″.

The second section 40″ of the dose dial sleeve 36″ is preferably of thesame outer diameter as the housing 2″. The second part 10″ of thehousing 2″ comprises an external sleeve portion 42″ surrounding acoaxial internal sleeve portion 44″. The external sleeve portion 42″ isclosed to the internal sleeve portion 44″ at a circular internal flangeportion 46″. The first section 38″ of the dose dial sleeve 36″ islocated within the second part 10″ of the housing 2″, between theexternal sleeve portion 42″ and the internal sleeve portion 44″. Aninner surface of the first section 38″ and the outer surface of theinternal sleeve portion 44″ are provided with interengaging features toprovide a helical thread 48″ between the internal sleeve portion 44″ ofthe second part 10″ of the housing 2″ and the dose dial sleeve 36″. Thishelical thread 48″ has the same lead as the internal thread of the drivesleeve 18″, as noted above. Within the helical track, a helical ribprovided on the inner surface of the dose dial sleeve 36″ may run. Thisenables the dose dial sleeve 36″ to rotate about and along the housing2″.

The second section 40″ of the dose dial sleeve 36″ is provided with anend wall 50″ adjacent its free end, which defines a central receivingarea 52″ between the end wall 50″ and the free end of the dose dialsleeve 36″. A through hole 54″ is provided in the end wall 50″. A dosebutton 56″ of generally “T” shaped configuration is provided, the head58″ of which is retained within the receiving area 52″ and the stem 60″of which is sized to pass through the through hole 54″. The stem 60″ ofthe button 56″ is provided with a plurality of fingers 62″ that aredeformable to pass through the through hole 54″ of the end wall 50″ onlyin the direction away from the free end of the dose dial sleeve 36″.

The drive sleeve 18″ is closed at its end remote from the externallythreaded section 24″ by an apertured end wall 64″ from which a pluralityof engagement features 66″ project external to the drive sleeve 18″.

A substantially U-shaped locking spring 68″ comprising first and secondlegs 70″, 72″ joined by a link portion 74″ is provided for longitudinalmounting on the exterior of the drive sleeve 18″. The link portion 74″is of a length which is substantially equal to the external diameter ofthe drive sleeve 18″. Each of the legs 70″, 72″ of the locking spring68″ terminates in a latch portion 76″, the function of which will bedescribed later.

When the device is assembled, the locking spring 68″ urges the dosebutton 56″ axially away from the piston rod 32″ and drive sleeve 18″,towards the inside of the end wall 50″ of the dose dial sleeve 36″. Inthis position, the dose button 56″ is locked with respect to rotationwith the dose dial sleeve 36″. The dose button 56″ is also permanentlylocked with respect to rotation with the drive sleeve 18″.

An outer surface of the first section of the dose dial sleeve 36″ isprovided with graphics 82″. The graphics are typically a sequence ofreference numerals. The housing 2″ is provided with an aperture orwindow 84″ through which a portion of the graphics, representing adosage value selected by the user, may be viewed.

The graphics 82″ may be applied to the dose dial sleeve 36″ by anysuitable means. The graphics 82″ may be printed directly on the dosedial sleeve 36″ or may be provided in the form of a printed labelencircling the dose dial sleeve 36″. Alternatively the graphics may takethe form of a marked sleeve clipped to the dose dial sleeve 36″. Thegraphics may be marked in any suitable manner, for example by lasermarking.

The external circumferential flange 26″ which projects from the drivesleeve 18″ is provided with a pair of diametrically opposed throughapertures 78″ sized to receive the corresponding latch portions 76″ ofthe locking spring 68″. A clicker projection 80″ from the outer edge ofthe flange 26″ is associated with each through aperture 78″.

In FIG. 18, the drug delivery device is provided with a filled cartridge4″. To operate the drug delivery device a user must first select a dose.To set a dose the dose dial sleeve 36″ is rotated with respect to thehousing 2″ until the desired dose value is visible through the window84″. The drive sleeve 18″ is linked to the dose dial sleeve 36″ andspirals out at the same rate during dialing. During the dialing of adose, the locking spring 68 is straight and urges the dose button 56″axially away from the piston rod 32″ and drive sleeve 18″, towards theinside of the end wall 50″ of the dose dial sleeve 36″, therebyproviding a clutch mechanism. The drive sleeve 18″ therefore rotatesover the toothed gear 22″ that is located inside it. The relativerotation between the drive sleeve 18″ and the housing 2″ causes anaudible confirmation of the dose being dialed by engagement of the twoclicker projections 80″ with the splines 30″ which extend along theinternal surface of the first portion 8″ of the housing 2″.

The limiting nut 28″ climbs up the drive sleeve 18″ in proportion to thedose dialed. The position of the limiting nut 28″, which only movesalong the external thread of the drive sleeve 18″ when there is relativerotation between the drive sleeve 18″ and the housing 2″, corresponds tothe amount of medicinal product remaining in the cartridge 4″.

Once a desired dose has been set (as shown for example in FIG. 19), todeliver the dose the user depresses the dose button 56″ to urge thebutton 56″ against the locking spring 68″. As the dose button 56″ pushesdown on the spring 68″, the clutch between the dose button 56″ and thedose dial sleeve 36″ is disengaged. The axial force applied from thedose button 56″ onto the dose dial sleeve 36″ causes the dose dialsleeve 36″ to spin into the housing 2″ on the helical thread between thedose dial sleeve 36″ and the housing 2″. The locking spring 68″ deformsand the legs of the spring move axially down the drive sleeve 18″. Thelatch portions 76″ of the locking spring 68″ engage in the throughapertures 78″ on the external flange 26″ which projects from the drivesleeve 18″ and maintain engagement between the clicker projections 80″of the flange 26″ with the grooves between the splines 30″, locking thedrive sleeve to the housing 2″ and preventing the drive sleeve 18″ fromrotation relative to the housing 2″ during dispensing of the dose. Thedrive sleeve 18″ is thus prevented from spinning and moves axially in,causing the toothed gear 22″ to rotate against the fixed rack 6″. Thetoothed gear 22″, together with the piston rod 32″ on which it ismounted, move along the rack 6″ a distance corresponding to one half ofthe distance by which the drive sleeve 18″ moves axially, creating a 2:1mechanical advantage. This has the two-fold benefit of allowing thedisplay on the dose dial sleeve 36″ to be larger for a given amount oftravel of the piston 14″ within the cartridge 4″, that is for a givenamount of medicament to be dispensed and secondly of halving the forcerequired to dispense the dose.

The piston rod 32″ is driven through the drive sleeve 18″ towards thefirst end of the drug delivery device, thereby to advance the cartridgepiston 14″ and expel the desired dose of medicinal product. The pistonrod 32″ continues to advance until the drive sleeve 18″ and dose dialsleeve 36″ have returned to their initial positions (FIG. 20).

It can be seen that the dose selecting means and the dose expellingmeans extend beyond a second end of the housing 2″ as the dose isselected and are returned within the housing 2″ as the selected dose isexpelled.

Further dosages may be delivered as required. FIG. 21 shows an exampleof a subsequently selected dosage. As noted above, the position of thelimiting nut 28″ along the external thread of the drive sleeve 18″corresponds to the amount of medicinal product remaining in thecartridge 4″, such that when the nut 28″ reaches the external flange 26″and can rotate no further this corresponds to no medicinal productremaining in the cartridge 4″. It will be seen that if a user seeks toselect a quantity of medical product greater than that remaining in thecartridge 4″, this cannot be done since when the nut 28″ stops rotatingagainst the drive sleeve 18″, the drive sleeve 18″ and the housing 2″will become locked together preventing rotation of the drive sleeve 18″and hence the dose dial sleeve 36″. This prevents the setting of alarger dose than the amount of medical product remaining within thecartridge 4″. FIG. 22 shows a drug delivery device according to thepresent invention in which the entire medicinal product within thecartridge 4″ has been expelled.

The illustrated embodiment of the device according to the inventionfurther comprises a maximum dosage dial end stop. When the dose dialsleeve 36″ is dialed fully out, the external flange 26″ on the drivesleeve 18″ engages the internal flange 46″ in the housing 2″. It will beseen that if the user tries to dial beyond the maximum dosage, thiscannot be done. When the drive sleeve 18″ stops rotating against thehousing 2″, the dose dial sleeve is also prevented from rotating. Thereaction between the external flange 44″ and the internal flange 86″indicates to the user that the maximum dose has been dialed.

1. A drive mechanism for use in a drug delivery device comprising: ahousing having a helical thread; a dose dial sleeve having a helicalthread engaged with the helical thread of the housing; a drive sleevehaving two radially extending flanges spaced a distance apart and havingan outer helical thread there between, where the drive sleeve isreleasably connected to the dose dial sleeve; a piston rod threadedlyengaged with the drive sleeve; and a clutch mechanism located betweenthe dose dial sleeve and the drive sleeve.
 2. A drive mechanism for usein a drug delivery device is provided comprising: a housing having ahelical thread, a dose dial sleeve having a helical thread engaged withthe helical thread of the housing; a drive sleeve releasably connectedto the dose dial sleeve; and a clutch mechanism located between the dosedial sleeve and the drive sleeve; wherein the clutch mechanism isconfigured such that, a) when the dose dial sleeve and the drive sleeveare coupled, both are allowed to rotate with respect to the housing; andb) when the dose dial sleeve and the drive sleeve are de-coupled,rotation of the dose dial sleeve with respect to the housing is allowed,while rotation of the drive sleeve with respect to the housing isprevented, whereby axial movement of the drive sleeve is allowed so thata force is transferred in the longitudinal direction to the a proximalend of the drug delivery device.
 3. The drive mechanism of claim 2further comprising a piston rod having a first external thread and asecond external thread, where the first external thread is threadedlyengaged with an insert, and where the second external thread isthreadedly engaged with an internal thread on the drive sleeve.
 4. Thedrive mechanism of claim 2 where the drive sleeve has two radiallyextending flanges spaced a distance apart and having an outer helicalthread there between and where the drive sleeve is releasably connectedto the dose dial sleeve.
 5. The drive mechanism of claim 4 furthercomprising a dose limiting mechanism.
 6. The drive mechanism of claim 5wherein said dose limiting mechanism is disposed between said firstflange and said second flange.
 7. The drive mechanism of claim 6 whereinsaid dose limiting mechanism comprises a nut threadedly engaged with theouter helical thread of the drive sleeve and is splined to an internalsurface of the housing to prevent the nut from rotating while allowingrelative longitudinal movement between the two flanges, whereby thelongitudinal movement is proportional to dispensed doses.
 8. A drivemechanism for use in a drug delivery device comprising: a) a mainhousing having a first end and a second end, a helical thread having afirst lead, an insert rotationally fixed to the housing having a threadwith a second lead; b) a dose dial sleeve having a helical threadengaged with the housing helical thread configured so that during doseselection the dose dial sleeve rotates and extends axially from thesecond end of the housing and during dose delivery rotates and movesaxially back into the housing; c) a tubular drive sleeve having aninternal surface and an outer surface having disposed thereon anintermediate thread, where the drive sleeve is releasably connected tothe dose dial sleeve through a clutch located between the dose dialsleeve and the drive sleeve and where the drive sleeve has an internalhelical thread having the same lead as the first lead; d) a piston rodhaving a first external thread and a second external thread, where thefirst external thread has a second lead that is different and ofopposite disposition than the first lead and is threadedly engaged withthe insert, and where the second external thread is threadedly engagedwith the internal thread of the drive sleeve; wherein, when the dosedial sleeve and the drive sleeve are coupled during dose section, bothare allowed to rotate with respect to both the housing and the pistonrod; and when the dose dial sleeve and the drive sleeve are de-coupledduring dose delivery, rotation of the dose dial sleeve with respect tothe housing is allowed, while rotation of the drive sleeve with respectto the housing is prevented, whereby axial movement of the drive sleeveis allowed causing the piston rod to rotate about the first externalthread and moving axially through the insert so that a force istransferred from the piston rod to a cartridge piston.
 9. The drivemechanism of claim 8 wherein the intermediate thread is disposed betweentwo radially extending flanges on the outer surface of the drive sleeve.10. The drive mechanism of claim 8 wherein the opposite disposition ofthe first external thread engaged with the insert prevents the pistonrod from moving during dose selection.